A method is known for regulating gene expression by establishing a specific binding between a nucleic acid of a specific gene and an oligonucleic acid or nucleic acid analog specific to the nucleic acid sequence of the gene to form a chemical bond (see, e.g., “Genome Chemistry,” edited by Sekine/Saitoh, Kodansha Ltd., 2003, Tokyo, Japan). In particular, recent studies have shown that depending on the structure of a chemical bond, a point mutation can be induced at the binding site (see, e.g., Nagatsugi, F., Sasaki, S., Miller, P. S., Seidman, M. M., Nucl. Acid Res, Vol. 31(6), e31 (2003)). Such a method for inducing point mutations in a sequence-specific manner is not only used as a biochemical experimental tool, but also has the possibility of being applicable to radical treatment of various diseases including gene abnormalities, thus receiving great attention in the fields of biochemistry, medicine and pharmacy.
On the other hand, nitric oxide (NO) plays an important role as an intracellular signal transmitter (see, e.g., L. J. Ignarro, Pharmacology & Toxicology, 67(1), 1, (1990)). In the body, S-nitrosothiol is believed to serve as a nitric oxide (NO) carrier (see, e.g., D. L. H. Wiliams, Acc. Chem. Res., 32, 869 (1999)). In addition to its role in signal transduction, nitric oxide (NO) also serves as an oxidizing agent in vivo to react with bases in DNA or RNA. It is therefore believed that NO may be responsible for point mutations. Moreover, chemical experiments have been found to cause non-specific mutations (see, e.g., J. L. Caulfield, J. S. Wishnok, S. R. Tannenbaum, J. Biol. Chem. 273(21), 12689 (1998); N. Y. Tretyakova, S. Burney, B. Pamir, J. S. Wishnok, P. C. Dedon, G N. Wogan, S. R. Tannenbaum, Mutation Research 447(2), 287 (2000)).
Recently, a report has been published on a method for DNA repair by DNA strand exchange, in which modified oligonucleotides are used to create a mismatch-containing double insert (M. D. Drury, E. B. Kmiec, Nucleic Acids Research 31(3), 899 (2003)). However, this method, which uses a model experimental system, provides low repair efficiency and also has many problems to be solved before being adapted for use in cellular systems.